Breast Flashcards
Which of the following statements about normal breast anatomy is true?
A. The breast typically contains 10 lobes.
B. Cooper ligaments are only found in the upper quadrants of the breast.
C. The upper inner quadrant of the breast contains the most breast tissue.
D. The tail of Spence extends across the anterior axillary fold.
D
The breast is composed of 15 to 20 lobes, which are each composed of several lobules.
Fibrous bands of connective tissue travel through the breast (Cooper suspensory ligaments), insert perpendicularly into the dermis, and provide structural support.
The mature female breast extends from the level of the second or third rib to the inframammary fold at the sixth or seventh rib. It extends transversely from the lateral border of the sternum to the anterior axillary line.
The deep or posterior surface of the breast rests on the fascia of the pectoralis major, serratus anterior, and external oblique abdominal muscles, and the upper extent of the rectus sheath.
The retromammary bursa may be identified on the posterior aspect of the breast between the investing fascia of the breast and the fascia of the pectoralis major muscles.
The axillary tail of Spence extends laterally across the anterior axillary fold.
(See Schwartz 10th ed., p. 500.)
Which of the following changes in the breast is NOT associated with pregnancy?
A. Accumulation of lymphocytes, plasma cells, and eosinophils within the breast.
B. Enlargement of breast alveoli.
C. Release of colostrum.
D. Accumulation of secretory products in minor duct lumina.
Answer: C
With pregnancy, the breast undergoes proliferative and developmental maturation.
As the breast enlarges in response to hormonal stimulation, lymphocytes, plasma cells, and eosinophils accumulate within the connective tissues. The minor ducts branch and alveoli develop.
Development of the alveoli is asymmetric, and variations in the degree of development may occur within a single lobule.
With parturition, enlargement of the breasts occurs via hypertrophy of alveolar epithelium and accumulation of secretory products in the lumina of the minor ducts. Alveolar epithelium contains abundant endoplasmic reticulum, large mitochondria, Golgi complexes, and dense lysosomes.
Two distinct substances are produced by the alveolar epithelium:
(1) the protein component of milk, which is synthesized in the endoplasmic reticulum (merocrine secretion); and
(2) the lipid component of milk (apocrine secretion),which forms as free lipid droplets in the cytoplasm.
Milk released in the first few days after parturition is called colostrum and has low lipid content but contains considerable quantities of antibodies.
(See Schwartz 10th ed.,p.501.)
The breast receives its blood supply from all of the following EXCEPT:
A. Branches of the internal mammary artery
B. Branches of the superior epigastric artery
C. Branches of the posterior intercostal arteries
D. Branches of thoracoacromial artery
Answer: B
The breast receives its principal blood supply from:
(1) perforating branches of the internal mammary artery;
(2) lateral branches of the posterior intercostal arteries; and
(3) branches from the axillary artery, including the highest thoracic, lateral thoracic, and pectoral branches of the thoracoacromial artery.
The second, third, and fourth anterior intercostal perforators and branches of the internal mammary artery arborize in the breast as the medial mammary arteries.
The lateral thoracic artery gives off branches to the serratus anterior, pectoralis major and pectoralis minor, and subscapularis muscles. It also gives rise to lateral mammary branches.
(See Schwartz 10th ed., p. 501.)
Which of the following statements is INCORRECT?
A. Level I lymph nodes are those that are lateral to the pectoralis minor muscle.
B. Level II lymph nodes are located deep to the pectoralis minor muscle.
C. Level III lymph nodes are located medial to the pectoralis minor muscle.
D. Level lV lymph nodes are the ipsilateral internal mammary lymph nodes.
Answer: D
Level I includes lymph nodes located lateral to the pectora- lis minor muscle;
Level II includes lymph nodes located deep to the pectoralis minor; and
Level III includes lymph nodes located medial to the pectoralis minor.
(See Schwartz 10th ed., p. 502.)
Concerning breast development before and during pregnancy, which hormonal activity pairing is INCORRECT?
A. Estrogen: Initiates ductal development
B. Progesterone: Initiates lobular development
C. Prolactin: Initiates lactogenesis
D. Follicle stimulating hormone: Cooper ligament relaxation
Answer: D
Estrogen initiates ductal development, whereas progesterone is responsible for differentiation of epithelium and for lobular development.
Prolactin is the primary hormonal stimulus for lactogenesis in late pregnancy and the postpartum period.
The gonadotropins luteinizing hormone (LH) and follicle- stimulating hormone (FSH) regulate the release of estrogen and progesterone from the ovaries.
In turn, the release of LH and FSH from the basophilic cells of the anterior pituitary is regulated by the secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus.
(See Schwartz 10th ed., pp. 503–504.)
Concerning gynecomastia, which of the following is true?
A. During senescence gynecomastia is usually unilateral.
B. During puberty gynecomastia is usually bilateral.
C. Is not associated with breast cancer except in Ehlers-Danlos patients.
D. Is classified as per a three-grade system.
Answer: D
In gynecomastia, the ductal structures of the male breast enlarge, elongate, and branch with a concomitant increase in epithelium.
During puberty, the condition often is unilateral and typically occurs between ages 12 and 15.
In contrast, senescent gynecomastia is usually bilateral.
Gynecomastia generally does not predispose the male breast to cancer. However, the hypoandrogenic state of Klinefelter syndrome (XXY), in which gynecomastia is usually evident, is associated with an increased risk of breast cancer.
Gynecomastia is graded based on the degree of breast enlargement, the position of the nipple with reference to the inframammary fold and the degree of breast ptosis and skin redundancy:
Grade I: mild breast enlargement without skin redundancy;
Grade IIa: moderate breast enlargement without skin redundancy;
Grade IIb: moderate breast enlargement with skin redundancy; and
Grade 3: marked breast enlargement with skin redundancy and ptosis.
(See Schwartz 10th ed., p. 505.)
Inflammatory conditions of the breast include all of the following EXCEPT
A. Necrotizing viral mastitis
B. Zuska disease (recurrent preductal mastitis)
C. Mondor disease (superficial breast thrombophlebitis)
D. Hidradenitis suppurativa
Answer: A
Zuska disease, also called recurrent periductal mastitis, is a condition of recurrent retroareolar infections and abscesses.
Hidradenitis suppurativa of the nipple-areola complex or axilla is a chronic inflammatory condition that originates within the accessory areolar glands of Montgomery or within the axillary sebaceous glands.
Mondor disease is a variant of thrombophlebitis that involves the superficial veins of the anterior chest wall and breast.
(See Schwartz 10th ed., pp. 506–507.)
Lesions with malignant potential include all of the following EXCEPT
A. Intraductal papilloma
B. Atypical ductal hyperplasia
C. Sclerosing adenosis
D. Atypical lobular hyperplasia
Answer: C
Sclerosing adenosis is prevalent during the childbearing and perimenopausal years and has no malignant potential.
Multiple intraductal papillomas, which occur in younger women and are less requently associated with nipple discharge, are susceptible to malignant transformation.
Individuals with a diagnosis of atypical ductal hyperplasia (ADH) are at increased risk or development of breast cancer and should be counseled appropriately regarding risk reduction strategies.
Atypical lobular hyperplasia (ALH) results in minimal distention of lobular units with cells that are similar to those seen in lobular carcinoma in situ (LCIS).
(See Schwartz 10th ed., pp. 509–510.)
Risk factors for the development of breast cancer include the following, except:
A. Early menarche
B. Nulliparity
C. Late menopause
D. Longer lactation period
Answer: D
Increased exposure to estrogen is associated with an increased risk for developing breast cancer, whereas reducing exposure is thought to be protective.
Correspondingly, factors that increase the number of menstrual cycles, such as early menarche, nulliparity, and late menopause, are associated with increased risk.
Moderate levels of exercise and a longer lactation period, actors that decrease the total number of menstrual cycles, are protective.
(See Schwartz 10th ed., p. 511.)
Drugs useful in breast cancer prevention include the following except
A. Raloxifene
B. Tamoxifen
C. Aspirin
D. Aromatase inhibitors
Answer: C
The P-2 trial, the Study of Tamoxifen and Raloxifene (known as the STAR trial), randomly assigned 19,747 postmenopausal women at high risk or breast cancer to receive either tamoxifen or raloxifene.
The initial report of the P-2 trial showed the two agents were nearly identical in their ability to reduce breast cancer risk, but raloxifene was associated with a more
favorable adverse event profile.
An updated analysis revealed that raloxifene maintained 76% of the efficacy of tamoxifen in prevention of invasive breast cancer with a more favorable side-effect profile.
Aromatase inhibitors (AIs) have been shown to be more effective than tamoxifen in reducing the incidence of contralateral breast cancers in postmenopausal women receiving AIs for adjuvant treatment of invasive breast cancer.
(See Schwartz 10th ed., p. 514.)
Which of the following is true regarding breast cancer metastasis?
A. Metastases occur after breast cancers acquire their own blood supply.
B. Batson plexus facilitates metastasis to the lung.
C. Natural killer cells have no role in breast cancer
immunosurveillance.
D. Twenty percent of women who develop breast carcinoma metastases will do so within 60 months of treatment.
Answer: A
At approximately the 20th cell doubling, breast cancers acquire their own blood supply (neovascularization).
Thereafter, cancer cells may be shed directly into the systemic venous blood to seed the pulmonary circulation via the axillary and intercostal veins or the vertebral column via Batson plexus of veins, which courses the length of the vertebral column.
These cells are scavenged by natural killer lymphocytes and macrophages. Sixty percent of the women who develop distant metastases will do so within 60 months of treatment.
(See Schwartz 10th ed., p. 518.)
All of the following are true concerning breast LCIS EXCEPT
A. Develops only in the female breast.
B. Cytoplasmic mucoid globules are a distinctive cellular feature.
C. Frequency of LCIS cannot be reliably determined.
D. The average age at diagnosis is 65 to 70 years.
Answer: D
LCIS originates from the terminal duct lobular units and develops only in the female breast. Cytoplasmic mucoid globules are a distinctive cellular feature.
The frequency of LCIS in the general population cannot be reliably determined because it usually presents as an incidental finding.
The average age at diagnosis is 45 years, which is approximately 15 to 25 years younger than the age at diagnosis or invasive breast cancer.
(See Schwartz 10th ed., p. 519.)
Which of the following concerning breast cancer staging is correct?
A. Stage I tumors have no metastases to either lymph nodes or distant sites.
B. Stage III tumors include some with distant metastases (M1 disease).
C. Inflammatory carcinoma is considered stage 4 disease.
D. N4 disease includes metastases to highest contralateral axillary nodes.
Answer: C
Factors that determine the type of therapy offered to patients after diagnosis o breast cancer include all of the following except
A. Whether or not a therapy has been proven effective in clinical trials
B. Stage of disease
C. General health of patient
D. Biologic subtype
Answer: A
Once a diagnosis of breast cancer is made, the type of therapy offered to a breast cancer patient is determined by the stage of the disease, the biologic subtype, and the general health status of the individual.
(See Schwartz 10th ed., p. 536.)
Which of the following statements about the management of ductal carcinoma in situ (DCIS) is true?
A. DCIS treated by mastectomy has a local recurrence rate of 2%.
B. Extensive DCIS should be treated with tamoxien followed by lumpectomy.
C. Specimen mammography is only useful for patients with small amounts of DCIS.
D. Postoperative tamoxifen is useful in DCIS patients whose tumors are estrogen-receptor (ER) negative.
Answer: A
Women with DCIS and evidence of extensive disease (>4 cm of disease or disease in more than one quadrant) usually require mastectomy.
For women with limited disease, lumpectomy and radiation therapy are generally recommended.
For nonpalpable DCIS, needle localization or other image-guided techniques are used to guide the surgical resection.
Specimen mammography is performed to ensure that all visible evidence of cancer is excised.
Adjuvant tamoxifen therapy is considered for DCIS patients with estrogen-receptor (ER)-positive disease.
The gold standard against which breast conservation therapy or DCIS is evaluated is mastectomy.
Women treated with mastectomy have local recurrence and mortality rates of <2%.
(See Schwartz 10thed.,p.537.)
All of the following are true about accelerated partial breast irradiation (APBI) EXCEPT
A. APBI is delivered in an abbreviated fashion and a
lower total dose than standard course of whole breast radiation.
B. Suitable patients for APBI include women older than
or equal to 60 years.
C. Suitable patients for APBI include patients whose
tumor margins are greater than or equal to 2 mm.
D. Suitable patients for APBI include those with multifocal disease.
Answer: D
Accelerated partial breast irradiation (APBI) is delivered in an abbreviated fashion (twice daily or 5 days) and at a lower total dose compared with the standard course of 5 to 6 weeks of radiation (50 Gray with or without a boost) in the case of whole breast irradiation.
The ASTRO guidelines describe patients “suitable” for APBI to include women older than 60 years with a unifocal, T1, ER-positive tumor with no lymphovascular invasion, and margins of at least 2 mm.
Finally, a group felt to be “unsuitable” for APBI includes those with
3 or 4 disease, ER-negative disease, multifocality, multicentricity, extensive lymphovascular invasion (LVI), or positive margins.
(See Schwartz 10th ed., p. 539.)
Patients not suitable for sentinel lymph node (SLN) biopsy include all of the following EXCEPT
A. Inflammatory carcinoma of the breast.
B. Prior axillary surgery.
C. Biopsy-proven distant metastases.
D. Lower inner quadrant of breast primary carcinoma.
Answer: D
Clinical situations where sentinel lymph node (SLN) dissection is not recommended include patients with inflammatory breast cancers, those with palpable axillary lymphadenopathy and biopsy-proven metastasis, DCIS without mastectomy, or prior axillary surgery.
Although limited data are available, SLN dissection appears to be safe in pregnancy when performed with radioisotope alone.
(See Schwartz 10th ed., p. 545.)
Which of the following is true concerning breast cancer during pregnancy?
A. Metastases to lymph nodes occur in approximately
75%o patients.
B. Approximately 50% of breast nodules developing
during pregnancy are malignant.
C. Mammography is especially useful in localizing small lesions.
D. There is risk of chemotherapy teratogenicity if used during the second, but not the third, trimester of pregnancy.
Answer: A
Breast cancer occurs in 1 of every 3000 pregnant women, and axillary lymph node metastases are present in up to 75% of these women.
Fewer than 25% of the breast nodules developing during pregnancy and lactation will be cancerous.
Mammography is rarely indicated because of its decreased sensitivity during pregnancy and lactation; however, the fetus can be shielded if mammography is needed.
Chemotherapy administered during the first trimester carries a risk of spontaneous abortion and a 12% risk of birth defects.
There is no evidence of teratogenicity resulting from administration of chemotherapeutic agents in the second and third trimesters.
(See Schwartz 10th ed., p. 554.)
Embryology of the breast?
At 5th-6th week AOG, 2 ventral bands of thickened ectoderm (mammary ridges and milk lines) are evident in the embryo. In most mammals, paired breasts develop along these ridges, which extend from the base of the forelimb (future axilla) to the region of the hind limb (inguinal area).
Accessory breasts (polymastia) or accessory nipples (polythelia) may occur along the milk line when normal regression fails. Each breast develops when an ingrowth of ectoderm forms a primary tissue bud in the mesenchyme. The primary bud, in turn, initiates the development of 15-20 secondary buds. Epithelial cords develop from the secondary buds and extend into the surrounding mesenchyme. Major (lactiferous) ducts develop, which open into a shallow mammary pit. During infancy, a proliferation of mesenchyme transforms the mammary pit into a nipple.
If there is failure of a pit to elevate above skin level, an inverted nipple results. This congenital malformation occurs in 4% of infants.
At birth, the breasts are identical in males and females, demonstrating only the presence of major ducts. Enlargement of the breast may be evident, and a secretion (“witch’s milk”) may be produced. These transitory events occur in response to maternal hormones that cross the placenta.
Discuss amastia.
Amastia is absence of the breast, which is rare and results from an arrest in mammary ridge development that occurs during the sixth fetal week.
Discuss Poland’s syndrome.
Poland’s syndrome consists of hypoplasia or complete absence of the breast, costal cartilage and rib defects, hypoplasia of the subcutaneous tissues of the chest wall, and brachysyndactyly.
Breast hypoplasia also may be iatrogenically induced before puberty by trauma, infection, or radiation therapy.
Discuss symmastia.
Symmastia is a rare anomaly recognized as webbing between the breasts across the midline.
How are staphylococcal breast abscesses managed versus streptoccocal breast abscesses?
Staphyloccocal breast abscesses are more often deep and localized. Initial management is antibiotics and repeated aspiration. Operative drainage is reserved for:
1) cases that do NOT resolve with repeated aspiration and antibiotics
2) other indications for I&D (thinning or necrosis of overlying skin)
3) biopsy of abscess cavity wall should be considered during I&D to rule breast CA in patients where antibiotics and drainage have been ineffective.
Streptococcal breast abscesses are more often diffuse. Initial management is IV antibiotics (penicillins or cephalosporins) and warm compress.
How do you manage noninfectious inflammation or milk stasis?
Epidemic puerperal mastitis is initiated by highly virulent strains of MRSA, transmitted via the suckling neonate. Purulent fluid may be expressed from the nipple.
Tx: Breastfeeding is stopped, antibiotics are started, and surgical therapy is initiated.
Nonepidemic (sporadic) puerperal mastitis refers to involvement of the interlobular connective tissue of the breast by an infectious process. The patient develops milk stasis and nipple fissuring, which initiates a retrograde bacterial infection.
Tx: Emptying of the breast using suction pumps shortens the duration of symptoms and reduces the incidence of recurrences. The addition of antibiotic therapy results in a satisfactory outcome in >95% of cases.
How do you manage Zuska’s disease?
Zuska’s disease, AKA recurrent periductal mastitis, is a condition of recurrent retroareolar infections and abscesses. Smoking has been implicated as a risk factor for this condition.
Tx: This is managed symptomatically with antibiotics coupled with incision and drainage as needed.
How do you manage mycotic infections of the breast?
Fungal infections of the breast are rare, and involve blastomycosis or sporotrichosis.
Intraoral fungi that are inoculated into the breast tissue by the suckling infant initiate these infections, which present as mammary abscesses in close proximity to the nipple-areola complex. pus mixed with blood may be expressed from sinus tracts.
Tx: Antifungal agents can be given for systemic (noncutaneous) infections.
Candida albicans affecting the skin of the breast presents as erythematous, scaly lesions of the inframammary or axillary folds. Scrapings show fungal elements (filaments and binding cells). Therapy involves removal of predispoing factors (maceration) and applying topical nystatin.
How do you manage Hidradenitis suppurativa?
Hidradenitis suppurativa is a chronic inflammatory condition that originates within the accessory areolar glands of Montgomery (NAC) or within sebaceous glands (axilla).
Women with chronic acne are predisposed.
May mimic Paget’s disease or invasive breast cancer. Often multifocal and contiguous in the axilla.
Tx: Antibiotics therapy with incision and drainage of fluctuant areas.
Excision of involved areas may be required– consider flaps and STSG for large areas of skin loss.
How do you manage Mondor’s disease?
Mondor’s disease AKA string phlebitis is a variant of thrombophlebitis that involves the superficial veins of the anterior chest wall and abreast. It involves a thrombosed vein presenting as a tender, cord-like structure.
Common veins include:
Lateral thoracic vein
Thoracoepigastric vein
Superficial epigastric vein
This is a benign and self-limiting disorder (4-6 weeks). But for an uncertain diagnosis or the presence of a mass adjacent to the tender cord, biopsy is indicated.
Tx: Anti-inflammatory meds
Warm compresses
When sx persist/refractory to tx, consider excision of involved vein segment.
ANDI Classification of Benign Breast Disorders for Early Reproductive Years?
Early Reproductive Years
15-25 years old
NORMAL Lobular development Stromal development Nipple eversion *Small fibroadenoma ≤1cm
DISORDER
Fibroadenoma ≤3cm
Adolescent hypertrophy
Nipple inversion
DISEASE Giant fibroadenoma >3cm Multiple fibroadenomas >5 in one breast Gigantomastia Subareolar abscess Mammary duct fistula
ANDI Classification of Benign Breast Disorders for Later Reproductive Years?
Later reproductive years
25-40 years old
NORMAL
Cyclical changes of menstruation
Epithelial hyperplasia of pregnancy
DISORDER
Cyclical mastalgia
Painful nodularity >1 week of the menstrual cycle
Bloody nipple discharge
DISEASE
Incapacitating mastalgia
ANDI Classification of Benign Breast Disorders for Involution?
Involution
35-55 years old
NORMAL
Lobular involution
Duct involution (Dilatation, Sclerosis)
Epithelial turnover
DISORDER Macrocysts Sclerosing lesions Duct ectasia Nipple retraction Epithelial hyperplasia
DISEASE
Periductal mastitis
Epithelial hyperplasia with atypia
Cancer risk associated with benign breast disorders and in situ carcinoma of the breast?
NO RISK
Nonproliferative lesions
Sclerosing adenosis
Intraductal papilloma
1.5-2-FOLD RISK
Florid hyperplasia
4-FOLD RISK
Atypical lobular hyperplasia
Atypical ductal hyperplasia
7-FOLD RISK
Ductal involvement by cells of atypical ductal hyperplasia
10-FOLD RISK
Lobular carcinoma in-situ
Ductal carcinoma in-situ
Nonproliferative breast disorders?
NONPROLIFERATIVE 70% of Benign Breast Conditions (No increased risk for cancer) 1) Cysts and apocrine metaplasia 2) Duct ectasia 3) Mild ductal epithelial hyperplasia 4) Calcifications 5) Fibroadenoma and related lesions
Calcifications associated with cancer?
1) Microcalcifications <0.5mm
2) Fine, linear calcifications, which may show branching
Proliferative breast disorders without atypia?
PROLIFERATIVE WITHOUT ATYPIA
1) Sclerosing adenosis
- Childbearing and perimenopausal years
- Distorted breast lobules
- In the context of multiple microcysts or a palpable mass.
2) Radial scars (≤1cm) and complex sclerosing lesions (>1cm)
- Imaging features of a radial scar will dictate the need for either a vacuum-assisted biopsy or surgical excision to exclude the possibility of a carcinoma.
3) Ductal epithelial hyperplasia
- Mild: 3 to 4 layers above the basement membrane
- Moderate: ≥5 layers
- Florid: ≥70% of a minor duct lumen (solid or papillary, 1.5-2 fold risk of CA)
4) Intraductal papillomas
- Arise in major ducts, in premenopausal women
- <0.5cm but may be as large as 5cm
- (+) nipple discharge
- attached to wall of involved duct by a stalk
- NO increased risk of CA, unless multiple
Differentiate adenomas/other lesions of the breast from fibroadenomas.
ADENOMAS
Adenomas of the breast are well-circumscribed and composed of benign epithelium with sparse stroma, which is the histologic feature that differentiates them from fibroadenomas.
They may be divided into:
1) tubular adenomas (young, nonpregnant women)
2) lactating adenomas (during pregnancy or postpartum)
HAMARTOMAS
Discrete breast tumors 2-4cm, firm, sharply circumscribed.
ADENOLIPOMAS
Sharply circumscribed nodules of fatty tissue that contain normal breast lobules and ducts.
Proliferative breast disorders with atypia?
ATYPICAL PROLIFERATIVE BREAST LESIONS
Have some of the features of carcinoma in situ, but either lack a major defining feature of carcinoma in situ or have the features in less than fully developed form.
1) Atypical ductal hyperplasia (ADH)
- appears similar to low-grade DCIS histologically
- monotonous round, cuboidal, or polygonal cells enclosed by basement membrane with rare mitoses
- ADH: ≤2-3mm
- DCIS: >3mm
- usually needs excision biopsy for diagnosis
- INCREASED RISK for development of breast CA
2) Atypical lobular hyperplasia (ALH)
- minimal distension of lobular units with cells similar to those seen in LCIS
- small monomorphic cells that distend the terminal ductal lobular unit
- LCIS
- in LCIS, the acini are full and distended while the overall lobular architecture is maintained).
- classic LCIS is not associated with a specific mammographic or palpable abnormality but is an incidental finding noted on breast biopsy.
- Pleomorphic LCIS is a variant– there can be calcifications or other mammographic changes that dictate the need for biopsy.
- classic LCIS is not treated with excision as the patient is at risk for developing invasive breast cancer in either breast, and therefore the patient is counseled regarding appropriate risk reduction strategies.
- Pleomorphic LCIS can be difficult to distinguish from high-grade DCIS, and there are some proponents who have suggested that patients with pleomorphic LCIS be managed similar to those with DCIS with attention to margins and consideration for RT in the setting of breast conserving treatment.
- the use of IHC for e-cadherin can help discriminate between LCIS and DCIS.
- -> In lobular neoplasias, such as ALH and LCIS, there is a lack of E-cadherin expression, whereas the majority of ductal lesions will demonstrate E-cadherin activity.
What is the clinical significance of sclerosing adenosis? How is this managed?
The clinical significance of sclerosing adenosis lies in its imitation of cancer. Excisional biopsy and histologic exam are frequently necessary to exclude the diagnosis of cancer.
The diagnostic workup for radial scars and complex sclerosing lesions frequently involves stereotactic biopsy.
Usually it is not possible to differentiate these lesions with certainty from cancer by mammographic features, so a larger tissue biopsy is recommended either by way of vacuum-assisted biopsy or an open surgical excisional biopsy.
The mammographic appearance of a radial scar or sclerosing adenosis (mass density with spiculated margins) will usually lead to an assessment that the results of a CNB specimen showing benign disease are discordant with radiography findings.
What is the difference between puerperal abscesses and subareolar abscesses?
Unlike puerperal abscesses, a subareolar abscess is usually unilocular and often is associated with a single duct system. Ultrasound will accurately delineate its extent.
Recurrent abscess with fistula is treated by fistulectomy and primary closure with antibiotic coverage (ie, young women with squamous metaplasia of a single duct).
When subareolar sepsis is diffuse rather than localized, or more than one fistula is present, total duct excision is the most expeditious approach (ie, older women with multiple ectatic ducts).
Antibiotic therapy is useful for recurrent infection after fistula excision, and a 2-4 weeks course is recommended before total duct excision.
Discuss nipple inversion.
More women request correction of congenital nipple inversion than for nipple inversion secondary to duct ectasia.
Although the results are usually satisfactory, women seeking correction for cosmetic reasons should always be made aware of the surgical complications of altered nipple sensation, necrosis, and fibrosis with nipple retraction.
Nipple inversion is a result of shortening of the subareolar ducts, hence a complete division of these ducts is necessary for permanent correction of the disorder.
Indications for FISTULECTOMY in recurrent subareolar sepsis?
1) Small abscess localized to one segment
2) Recurrence involving the same segment
3) Mild or no nipple inversion
4) Patient unconcerned about nipple inversion
5) Younger patient
6) No discharge from other ducts
7) No prior fistulectomy
Indications for TOTAL DUCT EXCISION in recurrent subareolar sepsis?
1) Large abscess affecting >50% of the areolar circumference
2) Recurrence involving a different segment
3) Marked nipple inversion
4) Patient requests correction of nipple inversion
5) Older patient
6) Purulent discharge from other ducts
7) Recurrence after fistulectomy
Hormonal and nonhormonal risk factors for breast cancer?
HORMONAL
1) Increased exposure to estrogen:
- Early menarche
- Nulliparity
- Late menopause
2) Older age at first live birth
3) Obesity
(Major source of estrogen in postmenopausal women is conversion of androstenedione to estrone by adipose tissue; hence obesity is associated with a long term increase in estrogen exposure.
NON-HORMONAL
1) Radiation exposure (esp during adolescence, a period of active breast development)
2) Alcohol intake (increases levels of estradiol)
3) Fatty food intake (increases serum estrogen levels)
Protective factors against breast cancer?
Factors that decrease the total number of menstrual cycles:
1) Moderate levels of exercise
2) Longer lactation period
3) Terminal differentiation of breast epithelium associated with a full-term pregnancy
Factors in the Gail Model for Risk Assessment in Breast Cancer?
1) Age
2) Age at menarche
3) Age at first live birth
4) Number of breast biopsy specimens
5) Any history of atypical hyperplasia
6) Number of first-degree relatives with breast cancer
A woman’s risk factors are translated into an overall risk score by multiplying her relative risks from several categories. This risk score is then compared to an adjusted population risk of breast cancer to determine a woman’s individual or absolute risk.
The output is a 5-year risk and lifetime risk of developing breast cancer.
How does the Claus model of breast cancer risk work?
Using data from the Cancer and Steroid Hormone Study (case-control), the Claus risk assessment model is based on assumptions about the prevalence of high-penetrance breast cancer susceptibility genes.
This incorporates more information about family history but excludes other risk factors. It provides individual estimates of breast cancer risk according to decade of life based on presence of first and second degree relatives with breast cancer and their age at diagnosis.
How does the BRCAPRO model of breast cancer risk work?
The BRCAPRO model is a Mendelian model that calculates the probability that an individual is a carrier of a mutation in one of the breast cancer susceptibility genes based on their family history of breast and ovarian cancer.
This is based on age-specific incidence curves for both mutation carriers and noncarriers.
How does the Tyrer-Cuzick model for breast CA risk work?
It attempts to utilize both family history information and individual risk information. It uses family history to calculate the probability that an individual carries a mutation in one of the breast cancer susceptibility genes, and then the risk is adjusted based on personal risk factors, including:
age at menarche parity age at first live birth age at menopause history of atypical hyperplasia or LCIS height BMI
Indications for the use of MRI in breast cancer screening?
At least 20-25% lifetime risk based on risk assessment tools, considering:
1) Family history of breast CA
2) BRCA mutation carriers
3) Family member with a BRCA mutation who has not been tested
4) Individuals receiving radiation to the chest between 10-30 years old
5) Individuals with a history of Li-Fraumeni syndrome, Cowden syndrome, Bannayan-Riley-Ruvacalba syndrome
6) With a first degree relative with one of these syndromes
MRI is an extremely sensitive screening tool that is not limited by the density of the breast tissue as mammography is; however, its specificity is moderate, leading to more false-positive events and the increased need for biopsy.
Side effects of tamoxifen?
DVT (1.6x more often) Pulmonary emboli (3x more often) Endometrial cancer (2.5x more often)
Are aromatase inhibitors more effective than tamoxifen?
Aromatase inhibitors (AIs) have been shown to be more effective than tamoxifen in reducing the incidence of contralateral breast cancers in postmenopausal women receiving AIs for adjuvant treatment of invasive breast cancer.
The American Society of Clinical Oncology recommends tamoxifen for chemoprevention in premenopausal or postmenopausal women and consideration for raloxifene or exemestane in postmenopausal women who are noted to be at increased risk of breast cancer.
What percentage of breast cancers are caused by germ line mutation inheritance?
Up to 5% of breast cancers are caused by inheritance of germ line mutations such as BRCA1 and BRCA2.
These are inherited in an autosomal dominant fashion with varying degrees of penetrance. They both function as tumor suppressor genes, and for each gene, the loss of both alleles is required for the initiation of cancer.
Discuss BRCA1.
BRCA1 is located on chromosome arm 17q, spans a genomic region of approximately 100 kilobases (kb) of DNA, and contains 22 coding exons for 1863 amino acids.
Germline mutations in BRCA1 represent a predisposing genetic factor in as many as:
- 45% of hereditary breast cancers
- at least 80% of hereditary ovarian cancers.
Female mutation carriers have been reported to have up to an 85% lifetime risk (for some families) for developing breast cancer and up to a 40% lifetime risk for developing ovarian cancer. The average lifetime risk is between 60-70%. Approximately 50% of children of carriers inherit the trait.
In general, BRCA1-associated breast cancers are invasive ductal carcinomas, are poorly differentiated, are in the majority hormone receptor negative, and have a triple receptor negative (immunohistochemical profile: ER-negative, PR-negative, and HER2-negative) or basal phenotype (based on gene expression profiling). BRCA1-associated breast cancers have a number of distinguishing clinical features, such as an early age of onset compared with sporadic cases; a higher prevalence of bilateral breast cancer; and the presence of associated cancers in some affected individuals, specifically ovarian cancer and possibly colon and prostate cancers.
The two most common mutations are 185delAG and 5382insC, which account for 10% of all the mutations seen in BRCA1. These two mutations occur at a 10-fold higher frequency in the Ashkenazi Jewish population than in non-Jewish Caucasians. The carrier frequency of the 185delAG mutation in the Ashkenazi Jewish population is 1% and, along with the 5382insC mutation, accounts for almost all BRCA1 mutations in this population. Analysis of germline mutations in Jewish and non-Jewish women with early-onset breast cancer indicates that 20% of Jewish women who develop breast cancer before age 40 years carry the 185delAG mutation. There are founder BRCA1 mutations in other populations including, among others, Dutch, Polish, Finnish, and Russian populations.
Discuss BRCA2.
BRCA2 is located on chromosome arm 13q, and spans a genomic region of approx. 70kb of DNA. The 11.2-kb coding region gontains 26 coding exons, and encodes a protein of 3418 amino acids.
It is postulated to play a role in DNA damage response pathways. BRCA2 messenger RNA also is expressed at high levels in the late G1 and S phases of the cell cycle.
The breast cancer risk for BRCA2 mutation carriers is close to 85%.
The lifetime ovarian cancer risk is lower than for BRCA1, but is still estimated to be close to 20%.
50% of children of carriers inherit the trait.
Unlike male carriers of BRCA, men with germline mutations in BRCA2 have an estimated breast cancer risk of 6% (100-fold increase over the risk in the general male population).
BRCA2 associated breast cancers are invasive ductal carcinomas, which are more likely to be well-differentiated and to express hormone receptors that are BRCA-1 associated.
BRCA2 associtated breast cancer has a number of distinguishing features:
- Early age of onset
- Higher prevalence of bilateral breast CA
- Presence of associated cancers in some affected individuals (ovarian, colon, prostate, pancreatic, GB, bile duct, stomach, melanoma)
Founder mutations identified in BRCA2 include:
- 6174delT mutation (Ashkenazi Jews) - 1.2% (60% of ovarian CA and 30% of early onset breast CA)
- 999del5 - Icelandic and Finnish populations
What is the four-step process to identifying BRCA Mutation Carriers?
- Obtain a complete multigenerational family history
- Assess appropriateness of genetic testing for a particular patients
- Counsel the patient
- Interpret testing results
Genetic testing should be offered only in conjunction with patient education and counseling, including referral to a genetic counselor.
A thorough and accurate family history is crucial, because 50% of women with a BRCA mutation have inherited the mutation from their fathers.
When is a hereditary risk of breast cancer considered?
If a family includes:
1) Ashkenazi Jewish heritage
2) A first degree relative with breast cancer before age 50
3) A history of ovarian cancer at any age in the patient or first or second degree relative with ovarian cancer
4) Breast and ovarian cancer in the same individual
5) 2 or more first or second degree relatives with breast cancer at any age
6) Patient or relative with bilateral breast cancer
7) Male breast cancer in a relative at any age
The threshold for genetic testing is lower in individuals who are members of ethnic groups in whom the mutation prevalence is increased.
What test is clinically available for analyzing BRCA mutations?
Gene sequence analysis
What is phenocopy?
A familial cancer is caused by an identifiable BRCA mutation, but an individual tested had sporadic cancer.
This is possible if the individual tested developed breast cancer close to the age of onset of the general population (age 60 years or older) rather than before age 50 years, as is characteristic of BRCA mutation carriers.
What is the false-negative rate for BRCA mutation testing?
<5%
What are the risk management strategies for BRCA1 and BRCA2 mutation carriers?
1) Risk-reducing mastectomy and reconstruction
2) Risk-reducing salpingo-oophorectomy
3) Intensive surveillance for breast and ovarian cancer
4) Chemoprevention
What are the screening recommendations for BRCA mutation carriers who do not undergo risk-reducing mastectomy?
1) Clinical breast examination every 6 months
2) Mammography every 12 months beginning at age 25
(The risk of breast CA in carriers increases after age 30)
3) Annual MRI in women with a 20-25% or greater lifetime risk of developing breast cancer (mainly based on family history), women with a known BRCA1 or BRCA2 mutation, those with a first degree relative with a BRCA1 or BRCA2 mutation and have not had genetic testing themselves, those treated with RT to the chest between 10-30 years old, and those with Li-Fraumeni/Cowden/Bannayan-Riley-Ruvacalba syndrome, or a first degree relative with one of these syndromes.
What is the risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers?
20-40% (10x higher than in the general population)
Risk-reducing salpingo-oophorectomy is a reasonable prevention option in mutation carriers. In women with a documented BRCA1 or BRCA2 mutation, consideration for bilateral risk-reducing salpingo-oophorectomy should be between 35-40 years old, and at the completion of childbearing.
Hormone replacement therapy is discussed with the patient at the time of oophorectomy.
What are recommendations for screening for mutation carriers who opt to defer risk-reducing surgery?
Yearly transvaginal ultrasound timed to avoid ovulation and annual measurement of serum cancer antigen 125 levels, beginning at age 25 years.
When do breast cancers acquire their own blood supply?
At approximately the 20th cell doubling, breast cancers acquire their own blood supply. Thereafter, cancer cells may be shed directly into the systemic venous blood to seed the pulmonary circulation via the axillary and intercostal veins or the vertebral column via Batson’s plexus of veins, which courses the length of the vertebral column.
When does implantation of metastatic foci occur in breast cancer?
After the primary cancer exceeds 0.5cm, which corresponds to the 27th cell doubling.
What is multicentricity?
The occurence of a second breast cancer outside the breast quadrant of the primary cancer (or at least 4cm away).
This occurs in 60-90% of women with LCIS, and 40-80% of those with DCIS.
LCIS occurs bilaterally in 50-70% of cases, while DCIS occurs bilaterally in 10-20% of cases.
What is multifocality?
The occurence of a second cancer within the same breast quadrant as the primary cancer (or within 4cm of it).
Discuss LCIS.
LCIS originates from terminal duct lobule units, and develops only in the female breast.
It is characterized by distention and distortion of the terminal duct lobular units by cells that are large, but maintain a normal nuclear to cytoplasmic ratio.
Cytoplasmic mucoid globules are a distinctive cellular feature.
Neighborhood calcification (LCIS may be observed in tissues with microcalcifications, but the calcifications associated with LCIS typically occur in adjacent tissues) is a feature unique to LCIS.
LCIS usually presents as an incidental finding, diagnosed on average at 45 years, 12x more frequently in white women.
Invasive breast cancer develops in 25-35% of women with LCIS, with 65% of subsequent cancers becoming ductal in origin. Hence LCIS is regarded as a marker of increased risk rather than as an anatomic precursor.
Individuals should be counseled regarding their risk of developing breast cancer and appropriate risk reduction strategies.
Discuss DCIS.
Predominantly seen in female breast CA, DCIS accounts for 5% of male breast cancers.
It is characterized by a proliferation of minor ductal epithelium, resulting in papillary growths within the duct lumina. These papillary growths eventually coalesce and fill the duct lumina so only scattered rounded spaces remain between the clumps of atypical cancer cells, which show hyperchromasia and loss of polarity (cribriform growth pattern).
Eventually pleomorphic cancer cells obliterate the lumina and distend the ducts (solid growth pattern).
With continued growth, these cells outstrip the blood supply and become necrotic (comedo growth pattern). Calcium deposition occurs in necrotic areas and is a common feature on mammography.
The risk for invasive breast cancer is increased nearly fivefold in women with DCIS. The invasive CA are observed in the ipsilateral breast, usually the same quadrant as the DCIS (suggesting DCIS as an anatomic precursor).
DCIS Classification?
1) COMEDO
- High nuclear grade
- Extensive necrosis
- High DCIS grade
2) INTERMEDIATE
- Intermediate nuclear grade
- Focal or absent necrosis
- Intermediate DCIS grade
3) NONCOMEDO (solid, cribriform, papillary, or focal micropapillary)
- Low nuclear grade
- Absent necrosis
- Low DCIS grade
Discuss Paget’s disease.
Paget’s disease of the nipple frequently presents as a chronic, eczematous eruption of the nipple, which may be subtle but may progress to an ulcerated, weeping lesion.
It is usually associated with extensive DCIS and may be associated with an invasive cancer. A palpable mass may or may not be present. A nipple biopsy specimen will show a population of cells that are identical to the underlying DCIS cells (pagetoid features or pagetoid change).
Pathognomonic of this cancer is the presence of large, pale, vacuolated cells (Paget cells) in the rete pegs of the epithelium.
Paget’s disease may be confused with superficial spreading melanoma. Differentiation from pagetoid intraepithelial melanoma is based on the presence of S-100 antigen immunostaining in melanoma and carcinoembryonic antigen immunostaining in Paget’s disease.
Surgical therapy for Paget’s may involve lumpectomy or mastectomy, depending on the extent of involvement of the NAC and the presence of DCIS or invasive cancer in the underlying breast parenchyma.
Discuss invasive ductal carcinoma of the breast.
Invasive ductal carcinoma of the breast with productive fibrosis (scirrhous, simplex, NST), accounts for 80% of breast cancers, and presents with macroscopic or microscopic axillary lymph node mets in up to 25% of screen-detected cases, and up to 60% of symptomatic cases.
It occurs most frequently in perimenopausal or postmenopausal women in the 5th-6th decades of life as a solitary, firm mass. It has poorly defined margins, and its cut surfaces show a central stellate configuration with chalky white or yellow streaks extending into the surrounding breast tissues. The cancer cells often are arranged in small clusters and there is a broad spectrum of histologic types with variable cellular and nuclear grades.
75% of ductal cancers showed estrogen receptor expression.
Discuss medullary carcinoma of the breast.
Medullary cancer is a special type breast cancer, which accounts for 4% of all invasive breast cancers and is a frequent phenotype of BRCA1 hereditary breast cancer. Grossly the cancer is soft and hemorrhagic. A rapid increase in size may occur secondary to necrosis and hemorrhage.
On PE, it is bulky and often positioned deep within the breast. Bilaterality is reported in 20% of cases.
It is characterized microscopically by:
a) a dense lymphoreticular infiltrate composed predominantly of lymphocytes.
b) large pleomorphic nuclei that are poorly differentiated and show active mitosis
c) a sheet-like growth pattern with minimal or absent ductal or alveolar differentiation.
50% are associated with DCIS, which characteristically is present at the periphery of the cancer, and <10% demonstrate hormone receptors.
There is an intense lymphocytic response, hence benign or hyperplastic enlargement of the LN of axilla may contibute to erroneous clinical staging.
Patients have a better 5-year survival rate than those with NST or invasive lobular carcinoma.
Discuss mucinous carcinoma (colloid carcinoma).
Mucinous/colloid caricnoma accounts for 2% of all invasive breast cancers and typically presents in the older population as a bulky tumor. This is defined by extracellular pools of mucin, which surround aggregates of low-grade cancer cells.
Cut surface shows a glistening and gelatinous quality.
Fibrosis is variable, and when abundant it imparts a firm consistency to the cancer. Over 90% of mucinous carcinomas display hormone receptors.
Lymph node mets occur in 33% of cases, and 5 and 10 year survival rates are 73% and 59%, respectively.
Because of the mucinous component, cancer cells may not be evident in all microscopic sections, hence analysis of multiple sections is essential to confirm the diagnosis.
Discuss papillary carcinoma of the breast.
Papillary carcinoma of the breast is a special type cancer that accounts for 2% of all invasive breast cancers. It generally presents in the seventh decade of life, and occurs in nonwhite women.
These are small (<3cm) and are defined by papillae with fibrovascular stalks and multilayered epithelium. 87% express estrogen receptor.
They have frequent axillary mets and similar 5-10year survival rates to mucinous and tubular carcinoma.
Discuss tubular carcinoma of the breast.
Tubular carcinoma of the breast is another special type breast cancer and accounts for 2% of all invasive breast cancers. It is reported in as many as 20% of women whose cancers are diagnosed by mammographic screening and usually is diagnosed in the perimenopausal or early menopausal periods.
94% of tubular cancers express estrogen receptor.
10% of women with tubular carcinoma or invasive cribriform carcinoma will develop axillary lymph node metastases. However the presence of metastatic disease in one or two axillary lymph nodes does not adversely affect survival.
Distant metastases are rare in tubular carcinoma and invasive cribriform carcinoma. Long term survival approaches 100%.
Discuss invasive lobular carcinoma.
Invasive lobular carcinoma accounts for 10% of breast cancers. The histopathologic features include small cells with rounded nuclei, inconspicuous nucleoli, and scant cytoplasm. Special stains may confirm the presence of intracytoplasmic mucin, which may displace the nucleus (signet-ring cell carcinoma).
It is often multifocal, multicentric, and bilateral. Because of its insidious growth pattern and subtle mammographic features, invasive lobular cancers express estrogen receptor.
What is the difference between the craniocaudal (CC) view and mediolateral-oblique (MLO) view in a mammogram?
The MLO view images the greatest volume of breast tissue, including the upper outer quadrant and the axillary tail of Spence.
Compared with the MLO view, the CC view provides better visualization of the medial aspect of the breast and permits greater breast compression.
Other views include the 90deg lateral and spot compression views. The 90deg lateral view is used along with the CC view to triangulate the exact location of an abnormality. Spot compression may be done in any projection by using a small compression device, which is placed directly over a mammographic abnormality that is obscured by overlying tissues.
Mammography is also used to guide interventional procedures including needle localization and needle biopsy.
What mammographic features suggest a diagnosis of breast cancer?
1) A solid mass with/without stellate features
2) Asymmetric thickening of breast tissues
3) Clustered microcalcifications
4) Fine, stippled calcium in and around a suspicious lesion (50% of nonpalpable cancers)
NCCN Guidelines of screening breast cancer?
Normal-risk women ≥20 years old should have a breast exam at least every 3 years.
Starting at age 40 years, breast examinations should be performed yearly, and a yearly mammogram should be taken.
Screening mammography in women ≥50 years old has been noted to reduce breast cancer mortality by 20-25%.
What is the primary indication for ductography?
Nipple discharge, particularly when the fluid contains blood.
In ductography, cancers may appear as irregular masses or multiple intraluminal filling defects.
What is the role of ultrasonography in breast cancer?
Ultrasonography is an important method of resolving equivocal mammographic findings, defining cystic masses, and demonstrating the echogenic qualities of specific solid abnormalities.
On ultrasound, breast cysts are well-circumscribed, with smooth margins and an echo-free center.
Benign breast masses show smooth contours, round or oval shapes, weak internal echoes, and well-defined anterior and posterior margins.
Breast cancer characteristically has irregular walls, but may have smooth margins with acoustic enhancement.
Ultrasonography is used to guide fine-needle aspiration biopsy, CNB, and needle localization of breast lesions.
It has highly reproducible findings, and a high patient acceptance rate, but it does not reliably detect lesions ≤1cm in diameter.
It can also be used to image the regional lymph nodes in patients with breast cancer. (Sensitivity of 35-82%, and specificity of 73-97%).
What are the features of a lymph node with cancer?
Cortical thickening Change in shape of node to more circular appearance >10mm in size Absence of a fatty hilum Hypoechoic internal echoes
What is the role of MRI in breast cancer?
There is current interest in the use of MRI to screen breasts of high-risk women and women with a newly diagnosed breast cancer (MRI of the contralateral breast in women with a known breast CA has shown a contralateral cancer in 5.7% of these women).
Some scenarios where MRI may be useful include: evaluation of a patient with nodal mets from breast CA without an identifiable primary, to assess response to therapy in the setting of neoadjuvant systemic treatment, to select patients for partial breast irradiation techniques, and evaluation of treated breast for tumor recurrence.
From NCCN:
1) Useful in finding a primary breast lesion for patients with positive malignant axillary nodes, but negative clinical/imaging evidence of a primary tumor.
2) More accurate than mammogram in assessing extent of primary tumor in young women (dense breast tissue) and in diagnosis of invasive lobular carcinoma (>90% sensitivity).
3) Early detection of cancer in patients with BRCA mutation
What is the only oncogene that acts by inhibiting apoptosis rather than by directly increasing cellular proliferation?
Bcl-2
What is the Oncotype DX?
The Oncotype DX is a 21-gene RT-PCR-based assay approved for use in newly diagnosed patients with node-negative, ER-positive breast cancer.
A recurrence score is generated, and those patients with high recurrence scores are likely to benefit from chemotherapy.
Those with low recurrence scores benefit most from endocrine therapy and may not required chemotherapy.
The Trial Assessing Individualized Options for Treatment for breast cancer (TAILORx), designed to prospectively validate the use of 21-gene expression assay, have shown that patients with low recurrence score (0-10) have a low rate of local-regional and distant recurrence (98.7%) and very good overall survival at 5 years (98%) with endocrine therapy alone.
Retrospective analysis has also shown that the 21-gene recurrence score can be use in postmenopausal patients with ER-positive tumors and 1-3 involved axillary lymph nodes to predict the benefit of chemotherapy in addition to endocrine therapy.
What is the MammaPrint assay?
The MammaPrint assay uses a 70-gene expression profile to assess the risk of distant metastasis.
This is FDA approved for use in stage 1 or stage 2 node negative, ER-positive, or ER-negative breast cancers to identify patients with high or low risk of recurrence.
The prospective RASTER study reported that patients classified as low risk based on MammaPrint had a 97% distant recurrence-free interval at five years.
Results of the prospective MINDACT (MicroarrayInNode negative and 1-3 positive lymph node Disease may Avoid ChemoTherapy) trial were recently reported. The study was designed to assess whether the 70-gene expression assay would help avoid chemotherapy in patients considered clinically high risk but categorized as low genomic risk based on the assay. A 5-year rate of distant metastasis-free survival of >92% was identified as the cutoff for the benefit of chemotherapy.
Management of In Situ Breast Cancer (Stage 0) - LCIS?
Stage 0
LCIS (marker for increased risk, 9-fold increased risk for CA)
Goal: Prevent or detect at an early stage the invasive cancer that subsequently develops in 25-35% of women
DX:
1) History and PE
2) Diagnostic bilateral mammography
3) Observation with interval history and PE every 6-12months
4) Annual mammogram
TX: Advise regarding risk for Breast CA: - Chemoprevention - Bilateral total mastectomy - Consider tamoxifen
There is NO benefit to excising LCIS because the disease diffusely involves both breasts in many cases and the risk of developing cancer is equal for both breasts.
Management of In Situ Breast Cancer (Stage 0) - DCIS?
Stage 0
DCIS
(10-fold increased risk for CA)
DX:
1) History & PE
2) Diagnostic bilateral mammography
3) ER status
4) MRI as indicated
TX:
With evidence of extensive disease (>4cm or in >1 quadrant)
1) Mastectomy
2) Adjuvant tamoxifen therapy (if ER positive)
Limited disease
1) Lumpectomy
2) Radiation therapy
3) Adjuvant tamoxifen therapy (if ER positive)
Nonpalpable DCIS
1) Needle-localization/ image-guided techniques
2) Specimen mammography is performed to ensure that all visible evidence of cancer is excised.
3) Adjuvant tamoxifen therapy (if ER positive)
The gold standard against which breast conservation therapy for DCIS is evaluated is mastectomy. Women treated with mastectomy have local recurrence and mortality rates of <2%.
What is the ECOG 5194?
The Eastern Cooperative Oncology group (ECOG) initiated a prospective registry trial (ECOG 5194) to identify those patients who could safely undergo breast-conserving surgery without radiation.
Eligible patients were those with low or intermediate grade DCIS measuring 2.5cm or less, who had negative margins of at least 3mm and those with high grade DCIS who had tumors measuring 1cm or less with a negative margin of at least 3mm.
At a median follow up of 6.2 years, patients with low or intermediate grade DCIS had an in-breast recurrence rate of 6.1% while those with high-grade DCIS had a recurrence rate of 15.3%.
Approximately 4% of patients developed a contralateral breast cancer during follow up in both low/intermediate and high-grade groups.
This study identified an acceptable recurrence rate for those patients with low or intermediate grade DCIS treated with excision alone with a margin of at least 3mm. In contrast, patients with high-grade DCIS had an unacceptable high local recurrence rate.
What is the role of axillary staging in patients with DCIS?
The role of axillary staging in patients with DCIS is limited. One consideration is for patients undergoing mastectomy.
Since most lesions are currently diagnosed with needle core biopsy, there is about a 20% incidence of invasive breast cancer on final pathologic assessment of the primary tumor.
Since it is not feasible to perform sentinel node dissection after mastectomy, most surgeons will recommend the use of sentinel node dissection at the time of mastectomy for DCIS.
Management of Locoregional Invasive Breast Cancer (Stage I, IIA, IIB, IIIA*— T3N1-2M0)
DX
1) History & PE
2) Diagnostic bilateral mammogram
3) Breast UTZ as necessary
4) ER-PR status determination
5) HER2 status determination
6) Pathology review
TX:
1) Mastectomy with Axillary Staging (SLN dissection for clinically N0 patients– ie, Modified Radical Mastectomy)
or
2) Breast Conserving Surgery (Lumpectomy or Wide Excision + RT or + SLNB)
- Not advised in women who are known BRCA mutation carriers, due to high lifetime risk for development of additional breast cancers.
+
Reconstruction
If post-mastectomy RT is needed, a tissue expander can be placed at the time of mastectomy to save the shape of the breast and reduce the amount of skin replacement needed. The expander can be deflated at the initiation of radiation therapy to allow for irradiation of the chest wall and regional nodal basins. Removal of the tissue expander and definitive reconstruction, usually with autologous tissue, can proceed 6 months to 1 year after completion of RT.
Relative contraindications to breast conservation therapy?
1) Prior radiation therapy to the breast or chest wall
2) Persistently positive surgical margins after re-excision
3) Multi-centric disease
4) Scleroderma or lupus erythematosus
When should adjuvant chemotherapy be considered for breast cancer, based on the ASCO guidelines?
Adjuvant chemotherapy should be considered for patients with:
1) Positive lymph nodes
2) ER-negative disease
3) HER2-positive disease
4) Adjuvant! Online mortality >10%
5) Grade 3 node-negative tumors >5mm
6) Triple negative tumors
7) Lymphovascular invasion
8) Estimated distant relapse risk of >15% at 10 years based on the 21 gene recurrence score assay
NCCN:
1) >2cm tumor
2) Poor histologic & nuclear grade
3) Negative hormone receptors
4) High proliferative fraction
5) HER2 expression
6) All node positive tumors
When should adjuvant endocrine therapy be considered in patients with breast cancer?
Adjuvant endocrine therapy is considered for:
Hormone (+) cancers
(Aromatase inhibitor if patient is postmenopausal)
HER2/neu status is determined for all patients with newly diagnosed invasive breast cancer and when positive, should be used to guide systemic therapy recommendations.
Indications for total mastectomy in DCIS?
1) Diffuse, suspicious mammographic calcifications
2) Inability to obtain clear margins on wide excision
3) Poor cosmetic result
4) Contraindications to RT
5) Patient’s choice
Indications for RT post-mastectomy?
1) ≥ 4 positive nodes
2) >5cm tumors (T3)
3) Very aggressive histology (diffuse vascular invasion)
4) Extranodal extension
5) Positive surgical margins
6) Inflammatory breast cancer
7) Involvement of skin, pectoral fascia, or skeletal muscle
Management of Atypical Ductal/Lobular Hyperplasia?
Atypical ductal/lobular hyperplasia has a 4-fold increased risk for malignancy.
TX:
1) Wire-localized excisional biopsy
2) Start Tamoxifen 20mg/day x 5 years
Components of the Gail Model?
1) Age
2) Age at Menarche
3) Age at first live birth
4) Family history
5) Number of breast biopsies
Five-year survival rates for breast cancer, if treated?
Stage I: 95-100% Stage II: 80-90% Stage III: 50-70% Stage IV: 1-20% Tis: 98-100%
Candidates for skin-sparing mastectomy?
Skin-sparing mastectomy is the excision of nipple/areola complex + skin around biopsy site, + skin within 1-2cm of tumor margin. 5-10% of skin is removed. May include SLNB (if positive–> ALND).
Candidates:
1) Multicentric disease
2) Invasive CA with extensive intraductal component
3) T2 tumors with difficult to interpret mammograms
4) Central tumors requiring removal of nipple-areola complex
Candidates for nipple-sparing mastectomy?
1) No clinical involvement of NAC
2) <5cm tumor
3) Tumor-nipple distance ≥2cm
Indications for level I & II axillary dissection?
1) Clinically positive nodes at diagnosis, confirmed by FNAB or CNB
2) Sentinel nodes not identified
In the absence of gross disease in level II nodes, dissection should include tissue inferior to the axillary vein from the lat dorsi, laterally to the medial border of the pex minor.
Indications for preoperative systemic therapy?
1) Locally advanced or inoperable breast tumors (inflammatory breast CA)
2) N2-N3 disease
3) T4 tumors
4) Operable breast CA who are clear candidates for adjuvant chemotherapy, and desire BCT
5) Breast cancer subtype with high likelihood of response
Options for adjuvant endocrine therapy for POSTmenopausal women (early breast CA)?
1) Aromatase inhibitor x 5 year
2) Tamoxifen x 2-3 years followed by:
- AI x 5 years or
- Tamoxifen x 4.5-6 years followed by AI x 5 years or
- Tamoxifen x 10 years
Mechanism of action of Aromatase Inhibitors?
AIs block conversion of adrenally synthesized androgens to estrogen (final step to conversion to active form of the hormone).
Options for adjuvant endocrine therapy for PREmenopausal women (early breast CA)?
1) Tamoxifen x 5 years, with or without suppression (adjuvant) or
2) Ovarian suppression + AI x 5 years
Mechanism of action and dose of Tamoxifen?
Tamoxifen 20mg/tab OD
Tamoxifen is a competitive ER antagonist.
Side effects: Hot flushes, vaginal dryness/discharge, thromboembolic events, endometrial CA
Management of advanced locoregional breast cancer (Stage IIIA or IIIB)?
DX:
1) History & PE
2) CBC
3) Liver FT + Alk phos
4) Chest imaging
5) Pathology review
6) Pre-chemo ER/PR status, HER2 status
7) Diagnostic bilateral mammogram
8) UTZ as necessary
TX:
1) Neoadjuvant chemotherapy (Anthracycline based)
2) Modified Radical Mastectomy
3) Adjuvant RT
4) Endocrine/Trastuzumab therapy as warranted.
If no response to adjuvant tx:
1) Additional chemotx or
2) Preoperative RT
Surveillance/follow up for Stage I-III breast cancer?
1) History & PE
2) Mammogram annually
3) If on Tamoxifen: annual gynecologic assessment
4) If on AI: Bone health + bone mineral density tests
5) Active lifestyle, healthy diet, maintain IBW (20-25 BMI)
Management of metastatic or recurrent breast cancer (Stage IV)?
DX:
1) History & PE
2) CBC
3) LFTs
4) Chest CT
5) Bone Scan
6) X-ray of painful weight bearing bones
7) Biopsy documentation of mets if possible
8) ER-PR, HER-2 status
TX:
1) Endocrine treatment
2) Systemic chemotherapy
3) Bisphosphonates (Bone mets)
Management of Phyllodes Tumor?
DX:
1) History & PE
2) UTZ
3) Mammogram if ≥30 years old
4) Core needle biopsy
TX:
1) Wide excision
2) Mastectomy for larger lesions
Recurrence:
Positive Mets: Follow soft tissue sarcoma guidelines
Negative Mets: Re-excision with wide margins ≥1cm
Negative axillary staging, consider postop RT
Management of Paget’s disease of the breast?
Rare manifestation of cancer, neoplastic cells in the epidermis of the nipple-areolar complex. Presents with eczema, bleeding, ulceration, itching. Associated cancer in the breast elsewhere in up to 80-90% of cases.
DX:
1) History & PE and Imaging (+) for breast mass:
Core needle biopsy of lesion + full thickness skin
2) History & PE and Imaging (-) for breast mass:
Full-thickness biopsy
3) Biopsies (-) for CA, but (+) for Paget’s:
Breast MRI and tissue sampling
TX:
1) (-) Mass or imaging abnormality:
Central lumpectomy (NAC + margin of underlying breast tissue)
2) Mass in other part of the breast:
Removal of NAC + negative margins + BCS for peripheral CA
3) Mastectomy (if DCIS)
Management of breast cancer during pregnancy?
Breast cancer during pregnancy is often ALN-positive, larger primary tumor size, and often with poorly differentiated tumors.
DX:
1) History & PE of breast and lymph node status
2) Mammogram with shielding
3) Ultrasound of breast and LN
4) FNAB or CNB (preferred) with ER-PR/HER2 analysis
5) CXR with shielding, include FTs and renal FTs, CBC (T1-T2)
6) Add liver UTZ and thoracolumbar MRI without contrast (N+ or T3)
TX:
1) BCS (Lumpectomy/wide excision + RT; RT can be delayed to postpartum)
2) MRM
3) Chemotherapy: For 2nd and 3rd trimesters ONLY with fetal monitoring prior to each chemo (BUT NOT >35 weeks AOG to prevent bleeding)
CONTRAINDICATIONS
- Trastuzumab, RT, AI, Tamoxifen: ONLY POSTPARTUM
- SLNB: Contraindicated for <30 weeks AOG
- Chemotherapy: Contraindicated for 1st trimester and after 35 weeks AOG.
Management of Inflammatory Breast Cancer?
IBC presents as erythema and dermal edema of ≥1/3 of skin of breast. It is often ER-PR/HER2 +. Considered as IIIB, IIIC, or Stage IV (T4d), is comprises <3% of breast CA. It is caused by blockage of lymph by tumor emboli.
DX:
1) History & PE
2) CBC + Plt
3) Pathology review (ER-PR/HER2)
4) Diagnostic bilateral mammogram
5) UTZ & MRI as necessary
6) Mets workup: LFTs, Bone scan, Chest/Abd/Pelvic CT, PET/CT for equivocal findings
TX:
1) Neoadjuvant chemotherapy
2) Mastectomy (with I/II ALND, ie MRM)
3) RT
4) HER2 therapy if (+)
Contraindications to Sentinel Lymph Node dissection?
SLND is used to assess the regional LN in early breast cancer who are clinically node negative.
Contraindications to SLND:
1) Inflammatory breast CA
2) Palpable axillary lymph nodes
3) Biopsy-proven metastases
4) DCIS without mastectomy
5) Prior axillary surgery
Tumors in lateral breast are likely to have a false negative SLN.
BIRADS Scoring System?
0: Incomplete
1: Normal
2: Benign
3: Probably Benign
4: Possibly Malignant (Suspicious)
5: Malignant (Highly suspicious)
6: Malignant Tissue
Discuss classifications for endocrine status.
The binding of estrogen to its receptor induces PR expression. The presence of both receptors in a tumor indicates an 80% chance of a favorable response to endocrine therapy.
LUMINAL A (ER+ PR+ HER2-)
- low-grade, 40% of all breast CA
- good prognosis
- TX:
1) Premenopause: SERMs (Tamoxifen)
2) Postmenopause: AIs (Anastrozole, Exemestane, Letrozole)
LUMINAL B (ER+ PR+/- HER2+/-)
- higher grade, 20%
- poorer prognosis
- TX:
1) Tamoxifen (decreased response)
2) Chemotherapy (increased response to chemo)
HER2-ENRICHED (ER- PR- HER2+)
- High-grade, often node positive
- p53 mutations
- 10-15% of all breast CA
- TX: Trastuzumab, Pertuzumab, Lapatinib
BASAL-LIKE (ER- PR- HER2-)
- Triple negative
- High proliferation, BRCA dysfunction
- 15-20%
- Poor prognosis
- TX: Chemotherapy
What is the 21-gene assay?
Oncotype Dx (21-gene assay) is the only assay clinically validated, using a 21-gene recurrence score (RS) for:
1) Predicting the benefit of adding adjuvant chemotherapy to adjuvant endocrine therapy, to further reduce the risk of recurrence in women with HR-positive, HER2-negative and node-negative breast cancer.
2) Determining the prognosis in women with HR-positive, HER2-negative tumors treated with endocrine therapy alone by predicting locoregional and distant recurrence.
What is the 70-gene assay?
MammaPrint (70-gene assay) can identify a subset of patients who have a low likelihood of distant recurrence despite a high risk clinical features (based on tumor size, grade and nodal status).
What is Adjuvant! Online?
Adjuvant! Online is a validated computer-based model available to estimate 10-year DFS and OS that incorporates all of the above prognostic factors except for HER2 tumor status.
What are the RECIST Guidelines?
Response Evaluation Criteria in Solid Tumors (RECIST) was introduced in 2000 to standardize and simplify tumor response criteria.
V 1.1 (2020)
TARGET LESIONS
CR: Disappearance of all target lesions and reduction in the short axis measurement of all pathologic lymph nodes to ≤10 mm
PR: ≥30% decrease in the sum of the longest diameter of the target lesions compared with baseline
PD: ≥20% increase of at least 5 mm in the sum of the longest diameter of the target lesions compared with the smallest sum of the longest diameter recorded
or
The appearance of new lesions, including those detected by FDG-PET
SD: Neither PR nor PD
NON-TARGET LESIONS
CR: Disappearance of all non-target lesions and normalization of tumor marker levels
IR, SD: Persistence of 1 or more non-target lesions and/or the maintenance of tumor marker levels above normal limits
PD: The appearance of 1 or more new lesions or unequivocal progression
If patient has measurable disease, an increase in the overall level or substantial worsening in non-target lesions, such that tumor burden has increased, even if there is SD or PR in target lesions
If no measurable disease, an increase in the overall tumor burden comparable in magnitude with the increase that would be required to declare PD in measurable disease (eg, an increase in pleural effusions from trace to large, or an increase in lymphangitic disease from localized to widespread)
Appropriate candidates for initial endocrine therapy in stage IV breast CA patients?
Women with hormone receptor positive cancers with no immediate life-threatening disease (or visceral crisis) (ie, only bone or soft tissue mets, and those with limited visceral mets).
Indications for systemic chemotherapy in stage IV breast CA patients?
Women with hormone receptor-negative cancers, visceral crisis, and hormone-refractory metastases.
Agents given to women with bone metastases in stage IV breast CA?
Bisphosphonates
Anti-RANKL (Receptor Activator of Nuclear Factor Kappa-B Ligand) agent, Denosumab
How do you manage local-regional recurrence?
Women post-mastectomy:
- Surgical resection of local-regional recurrence and reconstruction
- Consider chemotherapy and antiestrogen therapy
- Adjuvant RT if no previous RT
Women post-lumpectomy/BCS:
- Mastectomy
- Reconstruction
- Consider chemo and antiestrogen therapy depending on hormone status and HER2 status of the tumor.
When is excisional biopsy used?
When needle biopsy results are discordant with imaging findings or PE.
What type of incision is recommended for excision biopsies in the lower half of the breast?
Radial incisions
Why are radial incisions not recommended for the upper half of the breast?
Because of possible scar contracture resulting in displacement of the ipsilateral nipple-areola complex.
Similarly, curvilinear incisions in the lower half of the breast may displace the NAC downward.
How many lymph nodes are needed to stage the axilla in SLN biopsy?
Studies have demonstrated that 98% of all positive SLNs will be recovered with the removal of 4 SLNs. Therefore, it is not necessary to remove greater than 4 SLNs for accurate staging of the axilla.
What is a skin-sparing mastectomy?
A skin-sparing mastectomy removes all breast tissue, NAC, and scars for prior biopsy procedures.
There is a recurrence rate of <6-8%, comparable to the long-term recurrence rates of standard mastectomy, when skin-sparing mastectomy is used for patients with Tis to T3 cancers.
What is a total (simple) mastectomy?
A total (simple) mastectomy without skin sparing removes all breast tissue, the NAC, and skin.
What is an extended simple mastectomy?
An extended simple mastectomy removes all breast tissue, the NAC, skin, and level I axillary lymph nodes.
What is a modified radical “Patey” mastectomy?
An MRM removes all breast tissue, the NAC, skin, and levels I, II, and III axillary lymph nodes.
The pectoralis minor divided and removed by Patey may be simply divided, giving improved access to level III nodes, then left in situ, or occasionally the axillary clearance can be performed without dividing pectoralis minor.
What is the Halsted radical mastectomy?
The Halsted radical mastectomy removes all breast tissue and skin, the NAC, the pectoralis major and minor muscles, and levels I, II, and III axillary lymph nodes.
The use of systemic chemotherapy and hormonal therapy as well as adjuvant radiation therapy for breast cancer have nearly eliminated the need for radical mastectomy.
What is nipple-areolar sparing mastectomy?
Nipple-areolar sparing mastectomy has been popularized over the last decade especially for risk-reducing mastectomy in high-risk women.
Factors for eligibility:
1) Tumor located >2 to 3cm from the border of the areola
2) Smaller breast size
3) Minimal ptosis
4) No prior breast surgeries with periareolar incisions
5) BMI <40kg/m^2
6) No active tobacco use
7) No prior breast irradiation
8) No evidence of collagen vascular disease
Anatomic boundaries of the modified radical mastectomy?
1) Anterior margin of the latissimus dorsi laterally
2) Midline of the sternum medially
3) Subclavius muscle superiorly
4) 2-3cm inferior to the inframammary fold inferiorly
Skin-flap thickness in MRM?
7-8mm inclusive of skin and telasubcutanea. May differ with body habitus.
Current recommendations for RT in Stage IIIA and IIIB breast cancer?
1) Adjuvant radiation therapy to the breast and supraclavicular lymph nodes after neoadjuvant chemotherapy, and segmental mastectomy with or without axillary node dissection
2) Adjuvant radiation therapy to the chest wall and supraclavicular lymph nodes after neoadjuvant chemotherapy and mastectomy with or without axillary lymph node dissection
3) Adjuvant radiation therapy to the chest wall and supraclavicular lymph nodes after segmental mastectomy or mastectomy with axillary lymph node dissection and adjuvant chemothearpy.q
Candidates for adjuvant chemotherapy?
1) Positive lymph nodes
2) HER2-positive disease
3) Adjuvant! Online greater mortality >10%
4) Grade 3 LN negative tumors >5mm
5) Triple-negative tumors
6) LV invasion
7) Estimated distant relapse risk of 15% at 10 years based on 21 gene recurrence score
8) Hormone receptor negative cancers >1cm
Adjuvant chemotherapy regimens for HER2-negative breast CA?
Preferred:
1) Dose dense AC –> Paclitaxel every 2 weeks
2) Dose dense AC –> Paclitaxel weekly
3) TC (T = docetaxel)
Others:
1) CMF
2) AC –> Docetaxel every 3 weeks
3) AC –> Paclitaxel weekly
4) TAC (T = docetaxel)
Adjuvant chemotherapy regimens for HER2-positive breast CA?
Preferred:
AC –> T + trastuzumab +/- pertuzumab (T = paclitaxel)
TCH (docetaxel, carboplatin, trastuzumab +/- pertuzumab
AJCC T Staging for Breast Cancer?
TX: Primary tumor cannot be assessed
T0: No evidence of primary tumor
Tis (DCIS): Ductal carcinoma in situ (DCIS)
Tis (Paget): Paget disease of the nipple not associated with invasive carcinoma and/or carcinoma in situ (DCIS) in the underlying breast parenchyma. Carcinomas in the breast parenchyma associated with Paget disease are categorized based on the size and characteristics of the parenchymal disease, although the presence of Paget should still be noted.
T1: Tumor ≤20mm in greatest dimension T1mi: Tumor ≤1mm T1a: Tumor >1mm but ≤5mm T1b: Tumor >5mm but ≤10mm T1c: Tumor >10mm but ≤20mm
T2: Tumor >20mm but ≤50mm in greatest dimension
T3: Tumor >50mm in greatest dimension
T4: Tumor of any size with direct extension to the chest wall and/or to the skin (ulceration or macroscopic nodules); invasion of dermis alone does not qualify as T4
T4a: Extension to chest wall, invasion/adherence to pex in absence of chest wall structures does NOT qualify as T4
T4b: Ulceration and/or ipsilateral macroscopic satellite nodules and/or edema (inc peau d’orange) of the skin that does not meet criteria for inflammatory carcinoma
T4c: Both T4a and T4b present
T4d: Inflammatory carcinoma
AJCC cN Staging for Breast Cancer?
cNX: Regional lymph nodes cannot be assessed (ie, previously removed)
cN0: No regional lymph node mets (by imaging or clinical exam)
cN1: Metastases to movable ipsilateral level I, II axillary lymph nodes
cN1mi: Micrometastases
cN2: Mets in ipsilateral level I, II axillary LNs that are clinically fixed or matted; or in ipsilateral internal mammary nodes in the absence of axillary LN mets
cN2a: Mets in ipsilateral level I, II axillary LN fixed to one another (matted) or to other structures
cN2b: Mets only in ipsilateral internal mammary nodes in the absence of axillary LN mets
cN3: Mets in ipsilateral infraclavicular (level III axillary) LNs with or without level I, II axillary LN involvement; or in ipsilateral internal mammary LN with level I, II axillary LN mets; or mets in ipsilateral supraclavicular LN with or without axillary or internal mammary lymph node involvement
cN3a: Mets in ipsilateral infraclavicular lN
cN3b: Mets in ipsilateral internal mammary LNs and axillary LNs
cN3c: Mets in ipsilateral supraclavicular LNs
AJCC M Staging for Breast Cancer?
M0: No clinical or radiographic evidence of distance metastases
cMO(i+): No clinical or radiographic evidence of distant mets in the presence of tumor cells or deposits not larger than 0.2mm detected microscopically or by molecular techniques in circulating blood, bone marrow, or other nonregional nodal tissue in a patient without symptoms or signs of mets.
cM1: Distant mets detected by clinical and radiographic means
pM1: Any histologically proven mets in distant organs, or if in non-regional nodes, mets greater than 0.2mm.
